Effect of cigarette smoking on hepatic biotransformations in rats.

Adult male rats were nose-only exposed to cigarette smoke for 20 min each day for 6 months. Smoke inhalation was confirmed by urinary excretion of nicotine (4.5 micrograms/rat/day) and elevated blood carboxyhemoglobin (13.3%). Phenobarbital- and 3-methylcholanthrene-treated rats were included as positive controls for assessing hepatic enzyme induction. Cigarette smoke did not induce statistically significant alterations in hepatic enzyme activity when measured in vivo (pentobarbital sleep time and zoxazolamine paralysis time) or in vitro (oxidation, hydrolysis, glucuronidation, and glutathione conjugation). In some cases, the smoke-exposed rats did exhibit higher microsomal enzyme activity than did the controls, but this increase was also evident in the sham-control group. Therefore, these increases were attributed to stress and not to smoking per se. Additional evidence of stress associated with manipulation of the animals was the smaller percentage weight gains of the smoke-exposed and sham control rats over the 6-month period as compared to the controls (12, 35, and 50%, respectively). Smoking reduced hepatic glutathione by as much as 15%, but the glutathione transferase activity was not affected. These studies showed that chronic exposure of rats to cigarette smoke did not alter hepatic biotransformation processes, but do suggest that smokers may be less efficient than nonsmokers in the deactivation of xenobiotics by glutathione conjugation mechanisms.